Microfluidic methods in single cell biology

Stochastic variations within seemingly homogeneous cell populations determine the emergent properties of complex cellular systems such as biofilms, tumors, pluripotent stem cells, and multispecies ecosystems. The advent of microfluidic technologies, coupled with rapid advances in fluorescence-based molecular imaging and genomic, transcriptomic, and proteomic profiling techniques, has spurred a revolution in biological analysis at the level of single cells. Over the past decade, several microfluidic platforms have been developed that enable the isolation, enrichment, and biochemical or genetic analysis of individual cells with high spatiotemporal resolution in a fashion that is not achievable using macroscale methods. In sharp contrast to population-averaged measurements based on bulk-level techniques, microfluidic cell culture platforms permit the acquisition of multiparametric and high-content information while preserving the identity and monitoring the behavior of individual cells over time. In this way, microfluidics has ushered in new frontiers in single cell biology with a direct impact on applied and foundational studies in microbial ecology, systems biology, therapeutics development, and clinical diagnostics. In this chapter, we describe the transformative impact of microfluidics in single cell biology with particular emphasis on the following areas: (1) microfluidic bioreactors for cellular analysis in dynamically changing microenvironments, (2) microfluidic chips for in vitro drug screening, and (3) single cell confinement and isolation microchips for sorting and profiling rare or unculturable cells in complex environmental consortia.